This invention relates to virucides and in particular to a method of inactivating enveloped virus. In a composition of matter aspect, the invention relates to a pharmaceutical composition for use in the present method.
Viral infections have in the past been largely resistant to antibiotic therapy. In particular, herpes infections have proven to be especially refractory. Herpes virus belongs to the class known as 'enveloped virus", by which is meant those DNA or RNA virus having a lipoprotein envelope. Normally, the virus envelope is derived from host membrane components under the direction of viral protein. The class of enveloped virus includes herpes virus, e.g., herpes simplex 1 and 2; myxovirus, e.g., influenza virus; paramyxovirus, e.g., virus responsible for measles and mumps, and respiratory syncitial virus responsible for croup; corona virus, which is also implicated in the common cold; and toga virus, e.g., rubella virus and virus responsible for encephalitis and hemorrhagic fever.
Many compounds have antiviral or virustatic activity, i.e., they inhibit the spread of viral infection by inhibiting the replication of virus particles. However, they do not inactivate the virus. Acyclovir, 9-(2-hydroxyethoxymethyl)guanine, an antiviral drug which has recently been cleared by the FDA for use in treating herpes infections in humans, is a virustatic agent, but not a virucide.
Recent research has shown that certain lipophilic compounds inhibit replication of some enveloped virus in vitro. Sands, Antimicrobial Agents and Chemotherapy, 12, 523-528 (1977), discloses that various fatty acids can inhibit viral replication in bacteriophage, and that at least two modes of fatty acid inhibition can be involved. The first mode involves inactivation of the virus, i.e., virucidal activity. Oleic acid, a monounsaturated C.sub.18 fatty acid, was the most effective fatty acid tested for this property, but a C.sub.18 acid having two double bonds was essentially inactive. The second method is inhibition of replication, without killing the virus, i.e., anti-viral or virustatic activity. This phenomenon is related to the stage in the infectious cycle in which the fatty acid is added.
Reinhardt et al., J. Virology, 25, 479-485 (1978) disclose that unsaturated fatty acids can inhibit the viral replication of PR4 bacteriophage in vitro. The most effective acids were oleic acid and palmitoleic acid. Arachidonic acid (C.sub.20 tetraene) was moderately effective, but less effective than linolenic acid (C.sub.18 triene).
Kabara et al., Antimicrobial Agents and Chemotherapy, 2, 23-28 (1972) disclose that certain fatty acids inhibit the growth of gram-positive and gram-negative microorganisms, but no virus species were tested. Some saturated fatty acids had antibacterial activity, mono-unsaturated acids were more effective and dienoic acids were even more active, for C.sub.18 fatty acids. However, arachidonic acid was not inhibitory at the concentrations tested.
Sands et al., Antimicrobial Agents and Chemotherapy, 15, 67-73 (1979) disclose antiviral activity in vitro of C.sub.14-20 unsaturated alcohols having 1-4 double bonds, the most active being gamma-linolenyl alcohol (6,9,12-octadecatrien-1-ol), while a C.sub.20 tetraenyl alcohol had low activity. Lower antiviral activity in vitro was disclosed for saturated alcohols by Snipes et al., Ibid., 11, 98-104 (1977); and Snipes et al., Symp. Pharm. Effects Lipids (AOCS Monograph No. 5), 63-74 (1978).
A need continues to exist for a virucidal agent which is active against enveloped virus and which has very low toxicity, especially one that is a potent topical virucide against herpes virus.